We propose to investigate the use of biological molecules tagged with aminopolycarboxylate chelating groups as radiopharmaceuticals for the localization of tumors. The proteins serum albumin, fibrinogen, and antibody to carcinoembryonic antigen, and the glycopeptide antitumor antibiotic bleomycin will be conjugated with 1-(p-benzenediazonium)-ethylenediaminetetraacetic acid or one of several related molecules with different chemical specificity and chelating ability. The products will be labeled rapidly in solution by mixing them with radioactive metal ions such as In111, Ga67, Fe52, or Pb203. This separation of synthetic organic chemistry from radiochemistry simplifies the preparation and use of radiopharmaceuticals. In order to optimize labeling conditions and reagents, techniques such as gel filtration, gel electrophoresis, and circular dichroism measurements will be used to monitor changes in the physical properties of the labeled proteins. In vitro and in vivo biological studies including biological half-life, stability, organ distribution, tumor uptake, excretion, toxicity, pyrogenicity, sterility, immunogenicity, and biological activity will be carried out using tracer techniques and scintillation scanning in animals. The fate of the radiopharmaceuticals in vivo will be investigated by double-label experiments using C14 and radioactive metal ions. The objective of this project is to couple radionuclides with ideal physical properties to molecules with ideal biological properties for the localization of human cancer. BIBLIOGRAPHIC REFERENCES: "Covalent Attachment of Metal Chelates to Proteins: The Stability in Vivo and in Vitro of the Conjugate of Albumin with a Chelate of 111Indium," Claude F. Meares, David A. Goodwin, Charles S.-H. Leung, Amal Y. Girgis, David J. Silvester, Adrian D. Nunn, and Peter J. Lavender, Proc. Natl. Sci. USA, 73, 3803-3806, (1976). "Attachment of Fluorescent Metal Chelates to Macromolecules Using Bifunctional Chelating Agents," Charles S-H. Leung and Claude F. Meares, Biochem. Biophys. Res. Comm., 75, pp. 149-155 (1977).